Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and is used as part of highly active antiretroviral therapy (HAART) for the treatment of a human immunodeficiency virus (HIV) type 1. Efavirenz is also used in combination with other antiretroviral agents as part of an expanded postexposure prophylaxis regimen to prevent HIV transmission for those exposed to materials associated with a high risk for HIV transmission.
Efavirenz, is chemically described as (S)-6-chloro-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one, having the following structure:

Efavirenz product is first claimed in U.S. Pat. No. 5,519,021. The process disclosed in this patent involves reaction of racemic Efavirenz with optically active acid derivative followed by repeated purifications to give diastereomer. It is further subjected to hydrolysis in the presence of acid in n-butanol to give crude Efavirenz which is then recrystallized from hexane to give pure Efavirenz. However, this patent does not disclose any polymorphic forms of Efavirenz.
U.S. Pat. Nos. 6,939,964 and 6,639,071 claimed crystalline efavirenz polymorphic Forms I, II and III. U.S. Pat. No. 6,673,372 patent disclosed the crystalline efavirenz polymorphic Forms 1, 2, 3, 4 & 5. US 2006/0235008 claims different crystalline and amorphous forms of Efavirenz and process for the preparation thereof.
WO 2006/040643 application further discloses Efavirenz polymorphic Forms α, β, γ, γ1, γ2, ω, δ, N, O, P and processes for their preparation. The reproduction of examples for these polymorphs as disclosed in WO '643 is found to be very inconsistent. Also, it was found that some of these forms were never reproduced in our laboratory.
In light of above disadvantages in prior art processes, there is a need to prepare the pure and stable Efavirenz polymorphic forms by an efficient, economic and reproducible process, particularly to large scale preparation. Further, it should be suitable for handling and should have excellent physical and chemical stability, mainly to different heat and humidity conditions.